This study highlights the importance of global AS regulation during EMT in cancer progression and paves the way for further investigation into RNA regulation in EMT and metastasis.PPR proteins are a diverse family of RNA binding factors found in all Eukaryotic lineages. They perform multiple functions in the expression of organellar genes, mostly on the post-transcriptional level. PPR proteins are also significant determinants of evolutionary nucleo-organellar compatibility. Plant PPR proteins recognize their RNA substrates using a simple modular code. No target sequences recognized by animal or yeast PPR proteins were identified prior to the present study, making it impossible to assess whether this plant PPR code is conserved in other organisms. Dmr1p (Ccm1p, Ygr150cp) is a S. cerevisiae PPR protein essential for mitochondrial gene expression and involved in the stability of 15S ribosomal RNA. We demonstrate that in vitro Dmr1p specifically binds a motif composed of multiple AUA repeats occurring twice in the 15S rRNA sequence as the minimal 14 nucleotide (AUA)4AU or longer (AUA)7 variant. Short RNA fragments containing this motif are protected by Dmr1p from exoribonucleolytic activity in vitro. Presence of the identified motif in mtDNA of different yeast species correlates with the compatibility between their Dmr1p orthologues and S. cerevisiae mtDNA. RNA recognition by Dmr1p is likely based on a rudimentary form of a PPR code specifying U at every third position, and depends on other factors, like RNA structure.In eukaryotic cells, proteins that associate with RNA regulate its activity to control cellular function. To fully illuminate the basis of RNA function, it is essential to identify such RNA associated proteins, their mode of action on RNA, and their preferred RNA targets and binding sites. By analyzing catalogs of human RNA associated proteins defined by ultraviolet light (UV)-dependent and independent approaches, we classify these proteins into two major groups (1) the widely-recognized RNA binding proteins (RBPs), which bind RNA directly and UV crosslink efficiently to RNA, and (2) a new group of RBP-associated factors (RAFs), which bind RNA indirectly via RBPs and UV crosslink poorly to RNA. As the UV cross-linking and immunoprecipitation followed by sequencing (CLIP-Seq) approach will be ill-suited to identify binding sites of RAFs, we show that formaldehyde crosslinking stabilizes RAFs within ribonucleoproteins to allow for their immunoprecipitation under stringent conditions. Using an RBP (CASC3) and an RAF (RNPS1) within the exon junction complex (EJC) as examples, we show that formaldehyde crosslinking combined with RNA immunoprecipitation in tandem followed by sequencing (xRIPiT-Seq) far exceeds CLIP-Seq to identify binding sites of RNPS1. xRIPiT-Seq reveals that RNPS1 occupancy is increased on exons immediately upstream of strong recursively spliced exons, which depend on EJC for their inclusion.Background and objectives Studies of adults have demonstrated an association between metabolic acidosis, as measured by low serum bicarbonate levels, and CKD progression. We evaluated this relationship in children using data from the Chronic Kidney Disease in Children study. Design, setting, participants, & measurements The relationship between serum bicarbonate and a composite end point, defined as 50% decline in eGFR or KRT, was described using parametric and semiparametric survival methods. Analyses were stratified by underlying nonglomerular and glomerular diagnoses, and adjusted for demographic characteristics, eGFR, proteinuria, anemia, phosphate, hypertension, and alkali therapy. Results Six hundred and three participants with nonglomerular disease contributed 2673 person-years of follow-up, and 255 with a glomerular diagnosis contributed 808 person-years of follow-up. At baseline, 39% (237 of 603) of participants with nonglomerular disease had a bicarbonate level of ≤22 meq/L and 36% (85 of 237) of thow bicarbonate was associated with a lower risk of CKD progression. Fewer than one half of all children with low bicarbonate reported treatment with alkali therapy. https://www.selleckchem.com/products/n-acetyl-dl-methionine.html Long-term studies of alkali therapy's effect in patients with pediatric CKD are needed.Background and objectives Despite the presence of a universal health care system, it is unclear if there is intercenter variation in access to kidney transplantation in the United Kingdom. This study aims to assess whether equity exists in access to kidney transplantation in the United Kingdom after adjustment for patient-specific factors and center practice patterns. Design, setting, participants, & measurements In this prospective, observational cohort study including all 71 United Kingdom kidney centers, incident RRT patients recruited between November 2011 and March 2013 as part of the Access to Transplantation and Transplant Outcome Measures study were analyzed to assess preemptive listing (n=2676) and listing within 2 years of starting dialysis (n=1970) by center. Results Seven hundred and six participants (26%) were listed preemptively, whereas 585 (30%) were listed within 2 years of commencing dialysis. The interquartile range across centers was 6%-33% for preemptive listing and 25%-40% for listing afa written protocol was associated negatively with listing within 2 years of starting dialysis (odds ratio, 0.7; 95% confidence interval, 0.58 to 0.9). Conclusions Patient case mix accounts for most of the intercenter variation seen in access to transplantation in the United Kingdom, with practice patterns also contributing some variation. Socioeconomic inequity exists despite having a universal health care system.Although Juliet's claim, 'What's in a name? That which we call a rose by any other name would smell as sweet', may apply to family names, 'that which we call' embryos and procedures in reproductive genetics often smell sweet because the names were created to perfume not-so-sweet-smelling practices. Reproductive-genetic scientists and clinicians, including myself, have used perfumed names to make our research smell sweet for research ethics boards, research grant funders, government regulators, hospital administrators and the general public. The sweet-smelling names in reproductive genetics explored here include 'pre-embryo', preimplantation genetic 'diagnosis', 'normal' embryo, 'suitable' embryo, 'healthy' embryo, preimplantation genetic 'testing', 'non-invasive prenatal testing', 'donation', and most recently 'mitochondrial replacement therapy', a sweet-smelling name for germline nuclear transfer prohibited in antireproductive cloning legislation in most countries. In order for informed choices to occur for women who come to clinicians for information regarding reproductive genetics, and for transparency of scrutiny by research ethics boards, governmental regulators and the general public, it is essential that we consider the real meaning of sweet-smelling names in reproductive genetics.Research in the sciences of new-media arts aims to develop original research questions and borrows many different interdisciplinary research methodologies that often involve collaboration with professionals from non-art fields to provide real investigations. Over the last four decades, new-media arts provided unlimited strategies to integrate the laypeople into real interactive conversations allowing them to express their opinions and reflect their concerns regarding boundless scientific, environmental, political and ethical issues. Within this context, this article illustrates the parallel and growing attention to perform effective joint public engagement projects between both new-media arts and biological science domains and how biological science could benefit from the new-media arts projects to allow the laypeople to actively participate in decision-making processes regarding critical biological issues that seek more open and democratic biological investigations. This article, therefore, monitors the developments of public engagement as a concept in biological sciences and its practical principles, which they have been enhanced under the influence of today's new-media arts strategies of engagement. As an extension of the existed efforts, the article, finally, highlighted one of the most recent international conversation led by the author regarding an assumed new-media arts protocol to use stem cells in new-media arts labs and the role of such protocol to secure the highest standard level of public engagement, by which the laypeople could control and reshape the future of generative biology and personalised medicine.Empathy is a broad concept that involves the various ways in which we come to know and make connections with one another. As medical practice becomes progressively orientated towards a model of engaged partnership, empathy is increasingly important in healthcare. This is often conceived more specifically through the concept of therapeutic empathy, which has two aspects interpersonal understanding and caring action. The question of how we make connections with one another was also central to the work of the novelist E.M. Forster. In this article we analyse Forster's interpretation of connection-particularly in the novel Howards End-in order to explore and advance current debates on therapeutic empathy. We argue that Forster conceived of connection as a socially embedded act, reminding us that we need to consider how social structures, cultural norms and institutional constraints serve to affect interpersonal connections. From this, we develop a dispositional account of therapeutic empathy in which connection is conceived as neither an instinctive occurrence nor a process of representational inference, but a dynamic process of embodied, embedded and actively engaged enquiry. Our account also suggests that therapeutic empathy is not merely an untrainable reflex but something that can be cultivated. We thus promote two key ideas. First, that empathy should be considered as much a social as an individual phenomenon, and second that empathy training can and should be given to clinicians.One key factor that appears to be crucial in the rejection of quarantines, isolation and other social controls during epidemic outbreaks is trust-or rather distrust. Much like news reporting and social media, popular culture such as fictional novels, television shows and films can influence people's trust, especially given that the information provided about an epidemic disease is sometimes seen as grounded in 'scientific fact' by societies. As well as providing information on the 'correct science' behind disease transmission, spread and illness in films and literature, popular culture can also inform societies about how to feel and how to react during epidemics-that is to say create some expectations about the kinds of societal responses that could potentially occur. In this article we closely analyse three films that centre around epidemic diseases-Contagion (Steven Soderbergh, 2011), Blindness (Fernando Meirelles, 2008) and The Painted Veil (John Curran, 2006)-in order to highlight three categories of distrust that have recently been identified and conceptualised in broader discussions regarding trust and health institutional, social and interpersonal. These films raise two key issues about trust and social responses during epidemics. First, while certain aspects of trust are badly diminished during epidemic disease outbreaks, epidemics can also interact with pre-existing structural inequalities within society-based on race, gender or wealth-to create mixed outcomes of discord, prejudice and fear that coexist with new forms of cohesion. Second, the breakdown in trust seen at certain levels during epidemics, such as at the institutional level between communities and authorities or elites, might be mediated or negotiated, perhaps even compensated for, by heightened solidity of trust at the social level, within or between communities.